Genetic Variant NM_145201.6:c.894C>T (chr8-143576560-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_145201.6(NAPRT):c.894C>T(p.Pro298Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,610,952 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 57 hom., cov: 33)

Exomes 𝑓: 0.024 ( 539 hom. )

Consequence

NAPRT
NM_145201.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

5 publications found

Variant links:

Genes affected

NAPRT (HGNC:30450): (nicotinate phosphoribosyltransferase) Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).[supplied by OMIM, Mar 2008]

NAPRT links:

ENSG00000255050 (HGNC:):

ENSG00000255050 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=0.03 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6 link	c.894C>T	p.Pro298Pro	synonymous_variant	Exon 7 of 13	ENST00000449291.7	NP_660202.3	Q6XQN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7 link	c.894C>T	p.Pro298Pro	synonymous_variant	Exon 7 of 13	1	NM_145201.6	ENSP00000401508.2		Q6XQN6-1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3211

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.0548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0785

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0242

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0253

AC:

6234

AN:

246460

AF XY:

0.0258

show subpopulations

Gnomad AFR exome

AF:

0.00467

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0573

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0252

Gnomad OTH exome

AF:

0.0331

GnomAD4 exome

AF:

0.0243

AC:

35413

AN:

1458784

Hom.:

539

Cov.:

AF XY:

0.0245

AC XY:

17748

AN XY:

725612

show subpopulations

African (AFR)

AF:

0.00317

AC:

106

AN:

33440

American (AMR)

AF:

0.0139

AC:

619

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.0558

AC:

1449

AN:

25990

East Asian (EAS)

AF:

0.000177

AC:

AN:

39660

South Asian (SAS)

AF:

0.0199

AC:

1715

AN:

86046

European-Finnish (FIN)

AF:

0.0724

AC:

3763

AN:

51974

Middle Eastern (MID)

AF:

0.0556

AC:

320

AN:

5754

European-Non Finnish (NFE)

AF:

0.0233

AC:

25868

AN:

1111130

Other (OTH)

AF:

0.0260

AC:

1566

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1981

3962

5943

7924

9905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

970

1940

2910

3880

4850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0211

AC:

3208

AN:

152168

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1735

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.00424

AC:

176

AN:

41520

American (AMR)

AF:

0.0144

AC:

221

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0548

AC:

190

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.0178

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0785

AC:

832

AN:

10602

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0242

AC:

1642

AN:

67984

Other (OTH)

AF:

0.0237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

163

326

490

653

816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0224

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.5

(source)

DANN

Benign

0.66

PhyloP100

0.030

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over